How Antioxidant Nutrients Protect Against Heart Disease: Part II. The Role of Lipoproteins

Those seeking to prevent heart disease and live longer by relying on
low-cholesterol diets must be dismayed by the recent studies reporting that
even if they are successful in lowering their blood cholesterol, the average
lifespan will only be increased by eight months. [1] And that is the higher
projection of recent studies, the lower projection is less than three months
life expectancy increase. [2-4] These studies also show that if all causes
of heart disease were eliminated, the average lifespan would be increased
by only three years. The reason given is that the diseases of aging would
still limit lifespan.

That may be true if the approaches used to prevent heart disease would not
effect the aging of other organs and systems. Unfortunately, this is the
situation when only the cholesterol approach is implemented. However, one
very effective approach to preventing heart disease also protects against
the effects of aging and protects against many other diseases including
cancer. Antioxidant nutrients are our most effective weapons against heart
disease. They help us add ten to fifteen “good” years to our lifespans
by protecting us from the major killer diseases and postponing the diseases
of old age as well.

Thus, we have two distinct approaches and goals in preventing heart disease
— the cholesterol approach which produces limited results and the antioxidant
approach which produces many major health benefits. But this does not mean
that the two approaches are mutually exclusive. It is not a case of one
approach or the other. Dietary cholesterol and fats are certainly not THE
causes of heart disease but they are significant factors for the approximately
twenty percent lacking adequate lipoprotein compensatory mechanisms.

As we will see later, saturated fats, more than dietary cholesterol, have
some effect on blood cholesterol levels. This is because fats lead to decreased
LDL receptors in cells which result in more cholesterol remaining in the
blood instead of being pulled into the cells. Still, in the normal healthy
person, dietary fats do not have a significant effect on blood cholesterol

The classical risk factors all together — smoking, high blood pressure
and high blood cholesterol still account for less than half of heart disease
deaths. My point is that concentrating on the minor factors exposes you
to risk from the major cause of heart disease — antioxidant deficiencies!

You can actually combine the “prudent” measures with the antioxidant
“alternative ” measures for even greater protection if you so
choose. If you wish to eat low-cholesterol, low-fat diets — go ahead —
but also get a balance of vitamins and minerals. This is the theme of “The
New Supernutrition.” [5] However, many people will find that it is
a waste of time, effort and enjoyment to worry about cholesterol because
their bodies compensate for both dietary cholesterol changes and blood cholesterol
changes. The major compensatory mechanism is the lipoprotein cholesterol
transport system, which is the main topic of this article.

This article is the second of a series describing how antioxidant
nutrients prevent heart disease. The main emphasis of this article is building
the background needed to understand why cholesterol itself does not
initiate heart disease, but how it can become an important factor
when free radicals alter the cholesterol-carrying lipoproteins in the blood.
Part I of this series reviewed recent studies showing antioxidant nutrients
such as vitamin E, vitamin C, beta-carotene, selenium and pycnogenol do
indeed protect against heart disease. [6]

Of particular note was the multi-national World Health Organization study
by Dr. Fred Gey of the University of Bern (Switzerland) confirming vitamin
E deficiency is more closely linked to death from heart disease than high
blood cholesterol or high blood pressure. [7] Low vitamin E blood levels
could predict 62 percent of heart disease deaths, whereas all of the classical
risk factors combined explained less than half of heart disease deaths.

Vitamin E and the other antioxidant nutrients are protective in many ways
that involve both steps in the typical heart disease process. The first
step is plaque formation which narrows the artery openings. This is the
atherosclerosis step. The second step is when a blood clot forms in a coronary
artery that has been narrowed by atherosclerotic plaque. This is the typical
heart attack called coronary thrombosis. Figure 1 depicts the two components
of this common form of heart disease. [8]

As an example of antioxidant nutrient protection, vitamin E protects the
artery lining against injury, reduces the formation of compounds that can
cause plaque formation, improves the level of HDL cholesterol to carry away
cholesterol, and keeps the blood platelets from clumping so that clots are
not formed.

The anti-clotting factor is especially important, and I have discussed it
frequently. The first action most cardiologists take today is to prescribe
aspirin. Now aspirin doesn’t lower cholesterol or blood pressure, but studies
show that it reduces heart attacks by 30 to 50 percent by reducing blood
clotting. Unfortunately, aspirin affects the clotting process too much,
and some people develop serious gastrointestinal bleeding.

Vitamin E, on the other hand, helps repair blood platelets damaged by being
squeezed through narrowed arteries. Vitamin E does not interfere with the
same enzyme that aspirin interferes with which results in a longer time
required to form a clot. Thus, vitamin E normalizes clotting time
to prevent coronaries without causing internal bleeding. [9] Vitamin E works
in two ways to improve clotting. One way may be similar to the manner in
which aspirin works, but vitamin E is completely safe and far superior.

An interesting point is that this information has been elucidated since
my 1974 epidemiological study showing that vitamin E protects against heart
disease. [10-12] My data showed a very strong protective effect, but it
wasn’t until we learned much more about heart disease that we began to understand
the many ways in which vitamin E works.

This article will examine how preventing low-density lipoprotein from oxidizing
greatly reduces the formation of arterial plaque. However, first we should
review lipoproteins and their role in transporting cholesterol.


Cholesterol is a fatty material and is insoluble in blood. Most of the cholesterol
in the blood is present as a cholesterol ester. An ester is produced when
a free fatty acid — in this case, normally linoleic acid — is combined
with the cholesterol molecule. Both free cholesterol and cholesterol esters
are “fatty” type compounds.

Blood is primarily water containing lots of proteins and electrolytes. Remember
oil (fat) and water don’t mix. Chemists call fats, oils and other fatty
materials “lipids.” Soap can dissolve oil in water because one
end of a “soap” molecule is water-soluble and the other is fat-soluble.
Like dissolves like. The body overcomes the problem of transporting cholesterol
in blood, not by dissolving it in a soap, but by constructing special carriers.
These carriers have both lipid regions and protein regions, and are thus
called “lipoproteins.”

Lipoproteins are not compounds — they are macromolecular complexes. That
is, they are groups of different compounds arranged in a specific and orderly
fashion so as to accomplish a function. They are held together by patterns
of electronic charge distributions rather than being rigidly bonded. For
practical purposes, lipoproteins may be considered to be particles. The
important point is that lipoproteins are not specific compounds, but complexes
of compounds that act as a particle.

Lipoproteins typically consist of a lipid core of nonpolar triacylglycerol
and cholesterol esters surrounded by a layer of polar phospholipids, cholesterol
and apolipoproteins. Apolipoproteins will be discussed in the next section.
Figure 2 represents a “generic” lipoprotein. [13]

The hydrophobic (water-avoiding) “tails” of the outer lipid monolayer
are oriented to the oily interior of cholesterol esters as shown in figure
2. The polar hydrophilic (water-seeking) heads of the outer monolayer lipids
are exposed to the surface of the particle, allowing it to be solvated by

The various lipoproteins have different roles in transporting cholesterol,
triglycerides and other fatty compounds. A triglyceride is a fat that contains
three fatty acids attached to a glycerol molecule. All lipoproteins are
composed of the same types of compounds, but the percentage of each varies.

You know from experience that muscle (protein) is more dense than fat, and
that fat is less dense than water. Lean athletes do not float in water as
well as people with a large percentage of body fat. With lipoproteins, the
higher the percentage of fat (in the form of triglycerides) the lower the
density. Or putting it another way, the higher the percentage of protein
in a lipoprotein, the higher its density.

Lipoprotein density has been a classical way to describe the various lipoproteins.
They are readily separated in a centrifuge because of their greatly different
densities. There are six clinically significant lipoproteins, and four of
them are named according to their relative densities. The higher their density,
the more beneficial the lipoprotein.

The four common lipoproteins are, in descending order, high-density lipoprotein
(HDL), low-density lipoprotein (LDL), intermediate-density lipoprotein,
(IDL), and very-low-density lipoprotein, (VLDL). Figure 3 shows how the
percentage of protein increases as the diminishing lipid content also decreases
the size of the lipoprotein. Table 1 lists the composition of these lipoproteins.

Another clinically significant lipoprotein is lipoprotein(a) [Lp(a)] which
is closely related to LDL. Lp(a) is very important and will be discussed
in detail in Part IV of this series.

The sixth major lipoprotein is not involved in the transport of the cholesterol
that we are primarily concerned with in heart disease. This sixth lipoprotein
is called a “chylomicron” and is involved with transporting fats
and cholesterol from the intestine to the liver.


The protein portions of lipoproteins are called “apolipoproteins”or “apoproteins.” I prefer the term “apolipoprotein”
because it is a narrower description than the more general “apoprotein.”
HDL contains around 60 percent apolipoproteins, whereas the fat-filled chylomicrons
are only about one percent apolipoprotein. (See figure 3)

Apolipoproteins are designated first by the letter of the class they belong
to (A through E) and then by a Arabic or Roman numeral to designate the
sub-class. Table 2 describes nine common apolipoproteins. [13] Common usage
simply refers to apolipoproteins by the prefix “apo” followed
by the appropriate letter or letter/number designation. Thus, apolipoprotein
A and apolipoprotein B are usually called apoA and apoB, respectively.

Do not confuse “lipoprotein(a)” and “apolipoprotein A.”
The two are also written as Lp(a) and apoA. They are not the same critter.
Apolipoprotein A (apoA) is a component of Lipoprotein(a) [Lp(a)]. Hang in
there. I’ll clarify this when we discuss Lipoprotein(a) in Part IV.

Some apolipoproteins are integral components, whereas others are free to
transfer to other lipoproteins. The integral apolipoproteins usually penetrate
through the various regions of the complex, whereas the transferable lipoproteins
are usually peripheral to the surface. In figure 2, apolipoprotein C is
shown as a peripheral apolipoprotein, while apolipoprotein B is shown as
an integral apolipoprotein. [13]

Lipoprotein Function

As mentioned earlier, the various lipoproteins have different roles in cholesterol
transport. In this article, I will discuss only the roles of the four lipoproteins
named according to their densities. It is important to understand the role
of these cholesterol transporters, if we are to understand why the total
blood cholesterol measurement is not important in heart disease and why
other factors are important.

The liver converts excess food products into triglycerides and loads these
triglycerides into VLDL particles for transport to other cells. These cells
may “burn” the triglycerides for energy or store them as fat.
During transport, VLDL has some of its triglycerides broken down to free
fatty acids and glycerol by an enzyme called lipoprotein lipase, and a helper
protein called apoC-2.

Cholesterol is also loaded into VLDL by the liver. The cholesterol is either
manufactured by the liver or absorbed from food. If more cholesterol is
returned to the liver by lipoproteins, then the liver decreases its own
cholesterol production.

In a process that is unimportant to us here, VLDL becomes a “VLDL remnant”
and then IDL. As depicted by figure 3, IDL is a smaller complex than VLDL,
but contains the same quantity of cholesterol. Thus, in comparison
to VLDL, IDL has a higher percentage of cholesterol. IDL also has
a smaller quantity of triglyceride and a lower percentage of triglyceride
than VLDL.

When still more triglycerides are removed, IDL becomes LDL. Relative to
VLDL, LDL is cholesterol-rich even though both contain about the same quantity.
The big difference is that triglycerides have been removed and the particle
has become smaller. See figure 3.

LDL contains apolipoprotein B-100 (apoB-100). I keep straight which apolipoprotein
goes with LDL by keying on “B” for “Bad” and with a
capital “B.” Typical LDL particles are about 22 nanometers in
diameter and contain about 1,500 molecules of cholesterol esters, surrounded
by a lipid sheath having approximately 800 molecules of phospholipids and
500 molecules of unesterfied cholesterol.

LDL carries its cargo to cell membranes. Receptors on the cell surface latch
on to the LDL particle and carry it through the membrane and into the cell
interior, where the LDL cargo is unloaded. After unloading its cargo, the
LDL particle is transported to lysosomes within the cell, which disassemble
the LDL into its unassociated components.

The LDL receptor is an important factor in this process and will be discussed
more fully in Part IV. It will suffice here to point out that the number
of LDL receptors on each cell determines how many LDL particles — with
their cholesterol cargoes — are removed from the blood. The number of LDL
receptors is partially dietary-dependent and partially genetic.

In Part IV, we will examine the role of diet in LDL receptor production
and its role in blood cholesterol level. But the important thing to keep
in mind here is LDL, LDL receptors and the amount of cholesterol carried
into the cells are only a part of the blood cholesterol transport story.
The role of HDL is more important as HDL is able to overcome the problems
caused by too many LDL particles and too much LDL-carried cholesterol.

HDL is produced in the liver and carried by the blood. HDL is a round, flat,
coin-like molecule when it leaves the liver. Its structure is flexible —
like an empty sack that can be filled. A filled HDL molecule is spherical
in shape.

Unlike LDL which has only a single apolipoprotein, HDL has two major apolipoproteins
and five minor apolipoproteins. The major HDL apolipoproteins are apoA-I
and apoA-II. The minor HDL apolipoproteins are apoC-I, apoC-II, apoC-III,
apoD and apoE. It will suffice if you can remember that HDL contains apoA
and LDL contains apoB.

HDL, like LDL, uses a receptor on the cell surface to help it work. The
mechanism of this receptor has only recently been elucidated. When HDL contacts
the HDL receptor on the cell surface, the HDL receptor sends chemical messengers
to the cell interior. These chemical messengers carry excess cholesterol
to the HDL receptor, which then loads the cholesterol into HDL. As the flat
HDL particle fills up with cholesterol, it swells and breaks contact with
the HDL receptor. This newly discovered process will be discussed in more
detail in Part IV.

Thus, the role of HDL is to scavenge for excess and unwanted cholesterol
and take it back to the liver so that the liver doesn’t have to make so
much cholesterol. If you picture LDL particles as delivery trucks toting
cholesterol to the cells and HDL particles as garbage trucks hauling cholesterol
away from the cells — an analogy that I originated in 1976 to help the
public visualize this process — you will be close enough. [8]

The practical lesson then seems to be that if you have enough HDL, then
it won’t matter how much LDL you have. However, there is a fly in the ointment!
If we only had LDL and HDL particles to deal with, then the HDL-to-LDL ratio
would be the determining factor in cholesterol build up. However, when LDL
particles become oxidized, we have a new problem. Oxidized LDL is a horse
of a different color than LDL.

Oxidized LDL is taken up by LDL receptors uncontrollably and contributes
to invasive foam cell production. Thus, oxidized LDL becomes a major cause
of plaque build up, independent of the otherwise prerequisite damage to
the artery lining. Now that we have isolated a significant factor in the
first step in the common form of heart disease, we can focus on preventing
this problem. The good news is that the antioxidant nutrients protect LDL
from being oxidized.

In Part III of this series, I will discuss oxidized LDL and antioxidant
protection in detail.


1. Goldman, Lee; Weinstein, Milton C. and Tsevat, Joel. Circulation (April

2. The Cholesterol Myth Moore, Thomas J. Atlantic Monthly 37-57 (September

3. Heart Failure Moore, Thomas J. Random House, NY (1989)

4. Rose, Geoffrey and Shipley, Martin. Lancet 335:275-7 (1990)

5. The New Supernutrition. Passwater, Richard A. Pocket Books, NY, (1991)

6. How Antioxidant Nutrients protect against heart disease: Part I. Passwater,
Richard A. Whole Foods ( ) – (April 1991)

7. Inverse correlation between plasma vitamin E and mortality from ischemic
heart disease in cross-cultural epidemiology. Gey, K. Fred; Puska, Pekka;
Jordan, Paul and Moser, Ulrich K. Amer. J. Clin. Nutr. 53:326S-334S (Jan.

8. Supernutrition For Healthy Hearts Passwater, Richard A. Dial Press, NY

9. Aspirin and Vitamin E: More than one way to protect against heart disease.
Passwater, Richard A. Wholw Foods 12-14 (June 1988)

10. Heart Study of 70-79 Year Olds. Passwater, Richard A. Prevention 28(2)
61-8 (Feb. 1976)

11. Heart Study of 60-69 Year Olds. Passwater, Richard A. Prevention 28(4)
107-113 (April 1976)

12. Heart Study of 50-59 Year Olds. Passwater, Richard A. Prevention 28(5)
111-5 (May 1976)

13. Harper’s Biochemistry, 21st Ed. Murray, R. K., et al., Appleton &
Lange, Norwalk, CT (1988)

All rights, including electronic and print media, to this article are copyrighted
to Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).

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Written by Richard A. Passwater PhD

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